In June, I continued to look at some of the responses to Vul and colleagues paper on fMRI. What I found interesting about these papers is that they address underlying statistical principles important not just for fMRI studies but also a lot of other research which involves looking at large amounts of data. Indeed it looks increasingly clear that statistics itself is undergoing big changes as scientists acquire ever larger quantities of data. Perhaps these changes in science parallel those in wider culture where in a relatively short space of time people have routinely acquired gigabyes of data in the form of films and music. So in the Vul study, some name calling in the field of fMRI has attracted a lot of attention but perhaps this ‘story’ has run so far because of the tacit acknowledgement that we are flooded with information and people have doubts about whether this is being managed effectively. Some of the most interesting comments I found in these articles were by statisticians who advised researchers to return to basics – don’t analyse data twice and make sure there is enough information there to be able to draw sensible conclusions. One author even went as far as to say that the smaller studies aren’t particularly helfpul.
In terms of psychotherapy/neuropsychology articles, I looked at some more of Winnicott’s papers. Winnicott was a paediatrician who developed his own interpretation of psychoanalytic theory from his clinical practice. In one of his papers, we get to see a case being managed at home in the 1950’s. It’s difficult to know how it would be managed today as this would depend to some extent on local service provision but the intensive non-pharmacological home treatment of a psychotic teenager by the family in conjunction with Winnicott was anxiety provoking to read particularly as there was no mention of a medical work-up although it seemed to work out in the end in this case (for the period of follow-up). In clinical varieties of transference, Winnicott manages to convey some dense philosophical and clinical concepts in a few pages which makes for tough reading. I get the impression of a very intelligent man who is constantly innovating and building his theoretical framework – putting the pieces of the jigsaw together. I also wonder at times why he seems to have been marginalised. I suspect that this is more to do with having a smaller sphere of social influence than Freud or Klein rather than any difficulties with the theory although I’ve only had some very rudimentary thoughts on why this might be. One thing which must count in Freud’s favour is the sheer volume of his output. I also had a look at some neuropsychological studies in Multiple Sclerosis and SLE where there is central nervous system involvement. These are complex areas at the interface of functional neuroanatomy and neuropsychology where as far as I can determine the interface is still far from being clearly delineated. There is much work that remains to be done on identifying neural correlates of psychological constructs due to a range of theoretical and pragmatic issues although these papers provide pointers in the right direction perhaps.
In terms of social psychiatry articles, I reviewed a few more Department of Health documents and as always am impressed by the logistics that are involved whether this be the involvement of large groups of stakeholders in the consultation process or a theoretical analysis of the impact that policies might have. The Dementia Care Strategy has received a lot of attention recently and rightly so as it is intended to improve services for people with dementia, an area that governments around the world are recognising as one of the biggest population health issues for the 21st century. What was also interesting to see that web 2.0 technology is being incorporated into nursing and medical school curriculum although this study focused on trends in the use of this technology on the basis of a survey rather than on the practical aspects of how these technologies can be adapted for medical education.
In the books section there was a mixture of psychological and neurobiology with Oliver Sacks bridging the two in Seeing Voices, a book about deaf people who use signing to communicate. Sacks in his usual engaging style takes us into the world of the deaf community which he is able to do because he has a talent for understanding other people’s experiences and for conveying this to the reader while at the same time giving us flashes of neurological insight which spin our perspectives around in an instant. McAlpines ‘Multiple Sclerosis’ is an impressive work highly organised and covering many areas of research and understanding of the illness which includes careful explanations of relevant physiology and immunology. Understanding MRI was another book I was impressed by, this time for the simplicity in the work which takes us through some of they physics of imaging through to the practical issues that influence the images produced with a conscious effort by the authors to involve as little maths as possible (although I think it’s perfectly reasonable to include maths in a book – perhaps in the appendix where the reader can consider it as optional). Waking dreams focuses on the imagination and as far as I understand has been quite influential.
Dharmendra Modha’s cognitive computing blog gives us insights into IBM’s blue brain project which aims in the longer term to make simulations of the human brain a reality and is a useful way to keep a finger on the pulse of this area of computing. The other blogs reviewed contain useful educational resources for patients. Betts continues to look at Jungian Analytic Psychology and how it can be used for the analysis of a special form of literature – mythology and fairy tales. While often associated with childhood, Betts shows us how sophisticated these stories can be with multiple layers of subtlety that have the potential to give us insights into ourselves. In the news there were lots of interesting stories including a new screening test that has been trialled in Alzheimer’s Disease, the demonstration of benefits of Donepezil in people with mild cognitive impairment and depression, a csf peptide that might be a useful biomarker for Alzheimer’s Disease, the effects of sleep deprivation on brain activation (fMRI), the relation of the protein Rhes to Huntington’s Disease, a pilot study of Donepezil in Schizophrenia, parallels between Amitriptylline and nerve growth factor and further evidence supporting a relationship between dyslexia and the cerebellum.
Medical Articles
Medical Progress – Treatable Dementias
Correlations in Social Neuroscience Aren’t Voodoo
Correlations and Multiple Comparisons in Functional Imaging – A Statistical Perspective
Big Correlations in Little Studies
Discussion of Puzzlingly High Correlations in fMRI Studies of Emotion, Personality and Social Cognition
Psychology Articles
Dissociable Deficits in Multiple Sclerosis
Neuropsychological Impairment in SLE: A Comparison with Multiple Sclerosis
Symptom Tolerance in Paediatrics
A Case Managed at Home
Clinical Varieties of Transference
Social Psychiatry Articles
Web 2.0 Tools in Medical and Nursing School Curricula
Consultation Response and Analysis. National Dementia Strategy
Topic Selection Process for Technology Appraisals. A Consultation Document
Developing Services for Carers and Families of People with Mental Illness
Book Reviews
Understanding MRI
Waking Dreams
McAlpine’s Multiple Sclerosis. Third Edition
Seeing Voices
Blog Reviews
Dharmendra S Modha’s Cognitive Computing Blog
Braindisease’s Weblog
Marks Psychiatry
Buckeye Psychiatry, LLC
Podcast Reviews
John Betts on Jungian Analytic Psychology Episode #14
John Betts on Jungian Analytic Pyschology Episode #15
John Betts on Jungian Analytic Psychology Episode #16
John Betts on Jungian Analytic Psychology Episode #17
News Round-Up
Research in Mood Disorders
A small case-control study involving people with Bipolar Disorder, unaffected first-degree relatives and controls and using Diffuse Tensor Imaging found evidence of reduced structural integrity in the corpus callosum genu as well as the left superior and right inferior longitudinal fasciculus. There was also evidence of distributed areas of reduced structural integrity in unaffected relatives but it will be interesting to see the results of larger replication studies (Chaddock et al, 2009). In a study with 86 subjects, people with intermediate onset bipolar disorder were found to have increased a significant reduction in sulcal index in the right prefrontal cortex compared to controls and people with early onset bipolar disorder (Penttilä et al, 2009).
Research in Dementia
A recent study in Brain provided evidence for discriminating primary progressive aphasia (semantic type) from semantic dementia including changes in the middle and superior temporal gyri and inferior and medial temporal lobes (Mesulam et al, 2009). Putamen volume was found to be decreased in people with Frontotemporal dementia compared to people with Alzheimer’s Disease in one small structural MRI study (Looi et al, 2009). A retrospective post-mortem study provided further evidence of an overlap between Alzheimer’s Disease, Frontotemporal Dementia and Lewy Body Dementia using current diagnostic criteria (Piguet et al, 2009). A recent secondary analysis provided evidence that the Clinical Dementia Rating scale has remained valid for over three decades by correlating the scores with those of other psychometric measures (Williams et al, 2009). In a location-matching task – a visual task there was found to be less activation on fMRI in people treated with Galantamine for 3 months in this small study (Bokde et al, 2009). A swedish follow-up study of up to 40 years showed a significant increase in risk of all-type dementia in people with mid-life obesity (odds ratio 1.59 p=0.002) as well as an increased risk of Alzheimer’s Disease and Vascular Dementia (Hassing et al, 2009).
Soy isoflavones supplementation was associated with a significant improvement in spatial memory scores in a 12-week double-blind placebo-controlled cross-over trial involving 34 men and the authors suggest that this may be related to ‘oestrogen activation’ (Thorp et al, 2009). In a 10-year follow-up of people without dementia (the Baltimore Longitudinal Study of Aging), in the mild cognitive impairment group compared to the control group (1017 observations) there was found to be a significant differences in volume change in a number of areas including the hippocampus, superior parietal and frontal regions (Driscoll et al, 2009). Homocysteine levels at baseline were significantly associated with rate of decline of CAMCOG scores in a study involving 94 people with Alzheimer’s Disease over the age of 75. There were at least 3 6-monthly visits but participants could be included for up to 9.5 years and the authors suggest an intervention trial (Oulhaj et al, 2009). The authors of a small case (n=14) series of people with subcortical vascular dementia or Alzheimer’s Disease were able to identify cerebral microinfarcts more commonly in the latter group particularly in the occipital cortex. They hypothesise that the Amyloid plaques may predispose to cerebral microinfarcts (Okamoto et al, 2009).
In one post-mortem study all subjects with Lewy Bodies were retrospectively found to be functionally impaired although the calculation of an odds ratio was not possible (paper freely available here) (Byford et al, 2009). A type of swelling in the Purkinje cell axons referred to as a Torpedo was found to be elevated in people with Alzheimer’s Disease, Parkinson’s Disease and to a greater extent in cerebellar essential tremor in this post-mortem study (Louis et al, 2009). In an autopsy series (n=466) there was found to be no association between a measure of atherosclerosis in the circle of Willis (a marker of large vessel disease) and amyloid plaque in the frontal cortex or neurofibrillary tangles in the hippocampus (Luoto et al, 2009).
Research in Psychosis
Lurasidone was found to significantly improve Brief Psychiatric Rating Scale scores in people with schizophrenia and an acute psychosis in this 6-week randomised double-blind placebo-controlled trial (n=90 in each arm of the trial) in Japan (Nakamura et al, 2009). In a small open-label trial of augmentation with Donepezil in 28 people with schizophrenia there were found to be significant improvements in attention, memory and other cognitive measures (Chung et al, 2009). A naturalistic study (n=325) provided evidence that had greater efficacy for treatment of schizophrenia (using outcome measures including the PANSS) than chlorpromazine or haloperidol (Ravanic et al, 2009).
Research in Neurotic, Stress-Related and Somatoform Disorders
In a study which looked at 532 Norwegian people who had experienced the 2004 Tsunami in South-East Asia, the authors repeated measurements of the perceived life threat using a 5-point Likert scale which appears to have been designed for use in this study and which appears to have been validated within the study by correlating with other measures of danger perception. The authors describe an effect they refer to as recall amplification whereby the perceived threat of the original event increased with time. The authors conclude that their data suggests the current diagnostic criteria for PTSD should be reconsidered particularly as the recall amplification occured independently of the type of events or severity of PTSD symptoms* (Heir et al, 2009).
Research in Liaison Psychiatry
In a systematic review which included 27 studies comparing medical care in those with mental illness and 10 in those with substance misuse versus a control group the results were heterogenous. Some of the studies showed evidence of decreased medical care while others showed improvement in some areas (Mitchell et al, 2009).
Research in Learning Disability
In a large study which involved the use of 11,700 questionnaires for primary school children and the use of the Special Educational Needs register (and ICD-10 research criteria) in Cambridgeshire, the authors produced a revised prevalence estimate of 157 cases of autistic spectrum disorder in every 10,000 (Baron-Cohen et al, 2009).
News in Brief
A tool that takes roughly 5 minutes to complete has been validated in a study which was published in the BMJ and detected 93% of people with Alzheimer’s Disease. Further studies will be needed but this has potential as a clinically useful tool (This paper has been reported widely in the media e.g. here, here, here, here and here). Researchers in Japan have identified a new CSF peptide (APL1beta28) that is associated with brain levels of ABeta42. Another study looked at risk factors that discriminated those who developed cognitive impairment from those who did not and found evidence that protective factors included exercise, not smoking, education and living with a partner. Mild cognitive impairment was associated with a 50% increase in mortality compared to controls and Alzheimer’s Disease was associated with a 300% increase in mortality compared to controls in this longitudinal study with 10-year follow-up. Intermittent exotropia in boys was associated with a higher use of psychiatric services in one study and it will be interesting to see follow-up studies in this area to validate and further clarify the association. Preliminary evidence suggests a reciprocal relationship between APP and a protein called Reelin where higher levels of Amyloid Precursor Protein are associated with lower levels of Reelin.
The authors of a paper using data from the prospective DESCRIPA case-control study found evidence that the characteristic CSF biomarkers of Alzheimer’s Disease increased risk of progression up to 27-fold relative to controls. More details can be found here. Preliminary evidence from one study found that Donepezil was associated with a reduction in progression to Alzheimer’s Disease in people with MCI and depression compared to the control group. The control group took either placebo and Vitamin E and the same effect was not found in people with MCI without depression. Images have been captured of neuronal synapses forming with the involvement of a protein – Neuroligin. A recent potentially important finding is that the response of glial cells is reduced in Alzheimer’s Disease and if this is so it could play a role in the degenerative process. This study did however have a small sample size and the findings are in opposition to the main theory proposing an immune response triggered by the Beta Amyloid plaque. It will be interesting to see the results of larger replication studies. A new protein found in the brain – hypoxia upregulated mitochondrial movement regulator (HUMMR) has been associated with the movement of the mitochondria within cells under conditions of hypoxia. The positioning is suggested to play a role in the removal of calcium ions from the intracellular environment under such conditions and there may be a role in hypoxia secondary to stroke (although further research is needed). Diffraction enhanced imaging has been used to image finer anatomical detail in brains in vivo although the synchotron produced radiation is not viable for clinical use, the researchers state that it establishes the principle of using imaging to obtain highly detailed in vivo images of Alzheimer’s Disease related plaques.
A potentially important study for understanding Huntington’s Disease has been published. The study suggests that a protein ‘Rhes’ which is found only in the corpus striatum interacts with the mutant Huntingtin protein and reduces protein aggregates which subsequent leads to neurotoxicity. There may be an increased research interest in Rhes after these results. Further evidence has been found for the efficacy of Rapamycin in epilepsy and that this can reduce the changes (mossy fibre sprouting) that occur after a kainate challenge with increasing evidence that this is through an action on a regulatory protein. In one study nearly 93% of people with SLE were found to psychiatric conditions including anxiety and depression while in another study 63% of people with Rheumatoid Arthritis were found to have psychiatric conditions predominantly depression and as with previous studies was associated with the characteristics of RA.
A meta-analysis of 14 studies examining aetiology of depression found that variations in the serotonin transporter gene were not associated with an increased risk of depression (This is also covered over by the Neurocritic). An Australian study provided further evidence that depression significantly contributes to quality of life measures if people have concurrent somatic and medical conditions but also that dysthymia more significantly impacted on these quality of life measures. There was evidence of a correlation between dopamine metabolism and reduced grey matter density in people with fibromyalgia compared to controls in a small case-control study. There have been similar studies of this type before, but this 5-year follow-up study of 1238 older adults provided evidence that having a purpose in life was associated with a 50% reduction in mortality. An interesting nurse-led study characterised qualitative aspects of relationships and other changes that occur in people after they have developed a stroke and more information can be found here.
In a 2009 sleep conference a number of interesting findings were reported. Evidence that a number of interventions were effective in insomnia including meditation and CBT was provided while under certain circumstances there was an association between certain types of television and gaming use and insomnia or sleep debt. In a small fMRI study, people with chronic insomnia were found to have increased levels of activation particularly in visuospatial areas compared to a control group when tested on a working memory task***. In another study looking at adults with an average age of 40, less hours of sleep was associated with higher blood pressure. The researchers in a twin study found evidence that intrusive thoughts was associated with the stress-related insomnia. Increased sleep fragmentation was associated with a significant increase in mortality in this longitudinal study involving 5614 subjects. Older adults (aged 59-82) performed better than younger adults (aged 19-38) on cognitive tests after sleep deprivation in one study. From an evolutionary perspective there were a number of interesting findings that may be relevant to complex human phenomenon such as sleep. Thus in one study it was found that queen fire ants can sleep up to 9 hours a day whilst worker ants have small naps of up to a minute through the day suggesting a possible role for genetics in sleep patterns (although environmental cues may possibly play a role particularly as a recent study showed that ants respond to high pitched sounds which may be mimicked by other species and can produce marked behavioural responses). In another study it was found that rats were able to manage risk/reward so as to optimise reward in a task analogous to the Iowa gambling task. A study has recently provided preliminary evidence that paternal investment of resources (using a relevant outcome measure) is associated with the genetic similarity of the child.
One study provided evidence that naming objects may play a role in their perception. In this study people learnt how to group a novel class of object (designed for the study) based on similarities or name the objects. The latter group were better able to process new examples of these objects incorporating all of the features of this object much like one would with a face. More details are available here. In a prospective 5-year study of 906 older adults decreasing social activities (using a Likert Scale) were significantly associated with decreasing motor skills including strength and balance. A comparison of elderly people in the United States (from the Health and Retirement Study) and England (from the English longitudinal study of Aging) found that the American cohort performed significantly better on a number of cognitive measures than their counterparts in England. Members of the researcher team suggested that different treatment approaches to hypertension between the two countries may have contributed to these differences. The long and short versions of the period3 gene have been implicated in response to sleep deprivation and this study found that a different pattern of recruitment of cortical regions in a working memory task which the authors suggest as a potential intermediate step in the causal chain from gene to sleep deprivation response. A study has provided evidence that Amitriptylline binds to the tRKA and tRKB receptors causing dimerisation and results in outgrowth of neurites actions which parallel those of Nerve Growth Factor.
An MRI study (n=77 roughly) of people with dyslexia and a roughly equal number of controls without provided evidence of a difference between the groups in the right cerebellar declive and the right lentiform nucleus (the original article is freely available here). There have been previous studies which have implicated the cerebellum in language. The Canadian ‘Center for Addiction and Mental Health’ recently estimated that 1/25 of deaths globally are alcohol related (also covered here). Gaze is important in human social interactions and one study provided evidence that our interpretation of another person’s direction of gaze is influenced by our understanding of their internal state. These findings are relevant to social cognition theory. The authors of a recently published meta-analysis concluded that CBT was not effective in treatment of schizophrenia or in prevention of relapse in Bipolar Disorder and it will be interesting to see responses to this meta-analysis. A recent study provided evidence that Rhesus monkeys and humans share a similar mechanism for recognising faces by using a paradigm which involved the ‘Thatcher Effect’. This involves inverting facial features, the eyes and mouth and interferes with the task of facial recognition in both species.
In one study, students with higher levels of anxiety were found to spend more time focusing on irrelevant words (distractors) in a reading task. They were also given a maths task and it was found that the correct responses were similar in both the anxiety and control groups but the former group took longer to complete the tasks. (the article is freely available here).
Recent evidence supports an emerging theory of friendships – the Alliance Hypothesis. A previous theory states that people have friendships in which they count up the number of reciprocal gifts or tokens although there is a lot of data that doesn’t support this model. However the authors of the Alliance Hypothesis posit that people have friendships for times of conflict and that they prefer friends who are interested in their needs. A recent study suggests that people rank their friends similarly to how their friends rank them* . The authors of a model propose that marked changes in culture may more influenced by population density than the characteristics of the brain.
A slightly amusing finding occurred in one study looking at students who were using maths software packages for learning. When the students made mistakes they looked for problems with the computer software! In the National Longitudinal Study of Adolescent Health which included 2500 respondents there was found to be an association between carrier status for the MAOA low-activity-3-repeat allele and ‘gang membership’. It will be interesting to see the results of follow-up studies exploring this possible relationship further. In a study of violent recidivists, a lower glycogen level was associated with just under a third of the variation in recidivist offending. A systematic review of the cognitive effects of medications in older adults has been published. An online CBT package which utilises audio, visual and written material (but no clinician!) was used in one study in which participants enrolled for 5 weeks. 35% reported themselves as being ‘much or very much improved’. The authors of a expert-systems based computer program that generates music in response to the listener’s emotions are proposing to make the music copyright free (I haven’t yet been able to find the program online however and it looks as though it is in the prototype stage). It is tempting to speculate that such an approach could be adapted for therapeutic purposes for disorders of emotion and that absence of copyright fees might spur research in this direction. Three 35,000 year-old bone and ivory flutes have been found in Germany.
A study provided evidence that people conceptualise objects that are grouped together as more likely to share similar properties. Subjects were more likely to choose from a widely spaced group if they knew one or more of the objects had defective parts and more likely to choose from closely grouped objects if they knew one or more contained gift coupons**. Another study found that students were able to retain more information when presented with powerpoint slides without the use of animation to add information to the slide in stages. In a Swedish survey of 4500 people it was found that there were more older people (aged 65-79) online and that for all ages, 8% of online activity was spent in the ‘blogosphere’. A recent study involved 1224 bloggers and found that the main principles which bloggers valued were ‘truth, accountability, minimising harm and attribution’. Depending on the purpose of the blog, the priority of these values differed.
Notes
* However it can be argued that recall amplification may be secondary to recurring nightmares or flashbacks. The researchers noted for instance that if people had recall amplification, PTSD did not improve in severity between 6 and 24 months.
** From an evolutionary perspective, this complements the results of another study looking at chimpanzees and finding that they forage for fruits over wide distances and have good recall of trees that are bearing fruit in season. This ability to group objects would be helpful in scanning large areas for food and needing to economically remember where food of interest is located.
*** This may tie in with other research showing increased levels of metabolic activity in a ‘cortical hub’ in Alzheimer’s Disease.
References
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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.
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